Abstract
Composite Hemangioendothelioma (CHE) is a very rare, low-grade malignant vascular tumor. It is most commonly seen as one or more nodules on both sides of the fingers and toes. This tumor is rarely settled in the paraspinal muscles. The age of onset is usually between the ages of 21 and 72 (1), with average age of 39.5-41 years. The treatment is gross total removal of the lesion. The definitive diagnosis is made histopathologically. Our case was a 54-year-old male patient. He had a complaint of low back pain. A lumbar spine MRI revealed that it was settled in the right paravertebral muscle in the posterior vicinity of the transverse process between the right paraspinal muscle planes. The mass was removed grossly and totally. The diagnosis of CHE was made histopathologically. In this article, we presented a case of CHE a rare tumor settled in the paraspinal region a rare site.

Abstract
Spindle cell haemangioma (SCH), formerly known as spindle cell haemangioendothelioma, is a rare benign vascular tumour characterised by reactive vascular proliferation.1 The lesions mostly occur in the dermis and subcutaneous tissue of distal extremities. SCH is more common in children and young adults than other age groups, and it is equally prevalent in the sexes. Histologically, proliferating spindle cells and cavernous blood vessels constitute the structure of SCH. SCH can present as vascular tumours in Maffucci's syndrome (MS). MS should be suspected when multifocal SCHs appear with enchondromas. This article is protected by copyright. All rights reserved.

[Clinical and Ultrasonographic Features of Hepatic Infantile Hemangioendothelioma].

Sichuan Da Xue Xue Bao Yi Xue Ban. 2018 Jan;48(1):148-150

Authors: Wang H, Zhang H, Qiu TT, Peng YL

Abstract
OBJECTIVE: To investigate the clinical manifestations and ultrasound features of hepatic infantile hemangioendothelioma (IHE).
METHODS: This study retrospectively analyzed the clinical features and ultrasound characteristics of 8 patients of IHE,whose diagnosis was confirmed by surgery or liver biopsy from January 2010 to October 2016.
RESULTS: Among the eight IHE patients,the male-to-female ratio was 1:1,with the mean age ranged from 15 d to 3 yr.,of which six individuals were younger than 3 months old. Seven patients had single lesion and one case was multiple. The average size of the lesions was (8.2±1.0) cm diameter. Hypoechoic (4 cases) and echogenic lesions (3 cases) were shown by echography,the lesions border and morphology were clearly defined in 7 cases.Furthermore,internal echoes were mostly inhomogeneous (4 cases),and calcification or peripheral halo were even visible. Color Dopplar flow imaging (CDFI) showed internal visible line or more abundant blood flow signal in 6 cases,mainly to venous blood flow.
CONCLUSION: The age of onset for hepatic IHE seems less than three months. The echography with single lesion with clear border,regular solid mass or calcification in the tumor,should come to the possibility of IHE.

Abstract
The intravascular papillary endothelial hyperplasia (IPEH/Masson's tumor) is a rare benign tumor of the skin and subcutaneous vessels. We report, in four pediatric cases, clinical presentation, care (diagnostic and surgical) of Masson's tumor in children. Two boys (two years) and two girls (four and six years) showed a pain subcutaneous tumor (one to five centimeters). They were in the transverse abdominal muscle, between two metatarsals, at the front of thigh and in the axilla. Imaging performed (MRI, Doppler ultrasound) evoked either a hematoma, a lymphangioma or hemangioma. The indication for removal was selected from pain and/or parental concern. The diagnosis was histologically. A lesion persisted in residual form (incomplete initial resection), and is currently not scalable for eleven years.
DISCUSSION: This tumor is characterized by excessive proliferation and papillary endothelial cells in the vessels, following a thrombotic event. It is found mainly in adults (no specific age), and preferentially localizes in the face and limbs. The clinical differential diagnosis of this tumor is angiosarcoma. The imagery has not allowed in our series to diagnose but still essential to eliminate differential diagnoses. Only surgical excision with histological examination can differentiate. Our study emphasizes the possibility of pediatric cases with two cases of unusual locations (abdominal and axilla). Clinical presentations we met, now lead us to direct our histologist looking for a Masson tumor in any child with a subcutaneous tumor and/or intramuscular pain, sudden onset, and vascular appearance (after excluding an arteriovenous malformation).

Abstract
The paper describes a case of solitary epithelioid hemangioendothelioma concurrent with nodular parenchymal AL amyloidosis of the lung and Rosai-Dorfman disease in a 70-year-old woman. The core of the tumor was represented by bone tissue with dendriform ossification, as well as by amyloid that showed green apple birefringence at polarized light microscopy. The peripheral portions of the tumor and the myxohyaline stroma exhibited slit-like structures, epithelioid and fusiform cells with small cytoplasmic vacuoles. These cells expressed CD31, CD34, factor VIII, and cytokeratins 7 and 18. The Ki-67 proliferation index was 10%. S100- and CD68-positive histiocytes with the phenomenon of emperipolesis were revealed in the tumor and in the lymph nodes of the mediastinum and lung hilum. There was a positive reaction to immunoglobulin lambda light chains in the lymphocytic infiltration around amyloid clumps. The frequency of epithelioid hemangioendothelioma was less than 1 case per million people annually. We found only one case of its concurrence with pulmonary amyloidosis in the English-language literature. No relationship could be revealed between this tumor and Rosai-Dorfman disease.

Abstract
BACKGROUND: Vascular anomalies currently are classified according to their clinical and histological characteristics. Recent advances in molecular genetics have enabled the identification of somatic mutations in most types of vascular anomalies. The purpose of this study was to collate information regarding the genetic basis of vascular anomalies.
METHODS: The PubMed literature was reviewed for all citations that identified a mutation in a vascular anomaly between 1994 and 2017. Search terms included "vascular anomaly," "mutation," "gene," "hemangioma," "pyogenic granuloma," "kaposiform hemangioendothelioma," "capillary malformation," "venous malformation," lymphatic malformation," "arteriovenous malformation," and "syndrome." Articles that identified both germline and somatic mutations in vascular anomalies were analyzed. Mutations were categorized by type (germline or somatic), gene, signaling pathway, and cell(s) enriched for the mutation.
RESULTS: The majority of vascular anomalies had associated mutations that commonly affected tyrosine kinase receptor signaling through the RAS or PIK3CA pathways. Mutations in PIK3CA and G-protein-coupled receptors were most frequently identified. Specific types of vascular anomalies usually were associated with a single gene. However, mutations in the same gene occasionally were found in different vascular lesions, and some anomalies had a mutation in more than one gene. Mutations were most commonly enriched in endothelial cells.
CONCLUSIONS: Identification of somatic mutations in vascular anomalies is changing the paradigm by which lesions are diagnosed and understood. Mutations and their pathways are providing potential targets for the development of novel pharmacotherapy. In the future, vascular anomalies will be managed based on clinical characteristics and molecular pathophysiology.

Abstract
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood liver cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Abstract
OBJECTIVE: To ascertain the effectiveness of IHC markers of vascular origin like CD31, CD34, FLI1 and ERG in vascular soft tissue sarcomas including angiosarcomas, Kaposi sarcomas, epithelioid hemangioendothelioma and a non-vascular soft tissue sarcoma (Epithelioid sarcoma).
STUDY DESIGN: Descriptive study.
PLACE AND DURATION OF STUDY: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from 2011 to 2017.
METHODOLOGY: Diagnosed cases of angiosarcomas (n=48), epithelioid hemangioendothelioma (n=9), Kaposi sarcoma (n=9) and epithelioid sarcoma (n=20) were selected. Immunohistochemical staining as performed on formalin fixed paraffin embedded sections. The sections were stained for the following markers: CD34 (VENTANA clone Q Bend 10), CD31 (Leica clone 1 A 10), FLI1 (CELL MARQUE clone MRQ-1) and ERG (CELL MARQUE clone EP111).
RESULTS: A complete panel of CD34, CD31 and ERG was applied on 8/48 cases of angiosarcomas with triple positivity in 6 cases. Eight cases showed positivity for only CD31 and ERG and 2 cases showed positivity for only ERG. A complete panel of CD34, CD31 and ERG was applied on 3/9 cases of epithelioid hemangioendothelioma with positivity for all markers in 2 cases. Combined positivity for ERG and CD34 was seen in 2 cases and on 4 cases only CD31 immunohistochemical was solely applied with 100% positivity. FLI1 was not applied on any case. Among 9 cases of Kaposi sarcoma, ERG, CD34 and CD31 in combination were applied on only 1 case with triple positivity. Remaining cases show positivity for either CD34, CD31 or FLI1. Majority of cases of epithelioid sarcomas were diagnosed on the basis of cytokeratin and CD34 positivity with loss of INI1. The other vascular markers showed negativity in all cases.
CONCLUSION: Among these four markers, ERG immunohistochemical stain is highly effective for endothelial differentiation due to its specific nuclear staining pattern in normal blood vessel endothelial cells (internal control) as well as neoplastic cells of vascular tumors and lack of background staining.

Abstract
Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor that commonly affects lung, liver, and bone. Among all known EHE cases, only 20% have a pulmonary origin, with metastases to the pericardium occurring in less than 1% of these. Due to its low prevalence, variable presentation, and unknown latency period, a thoracic EHE diagnosis can be easily missed. This case outlines the unique pathologic features of EHE in a patient with cardiovascular disease, provides further insight into diagnosing a rare tumor, and provides a better understanding of the pathophysiology and progression of thoracic EHE.

Primary epithelioid angiosarcoma of right hip joint: A case report and literature review.

Medicine (Baltimore). 2018 Apr;97(15):e0307

Authors: Wang J, Zhao M, Huang J, Ang L, Zheng L

Abstract
RATIONALE: Epithelioid angiosarcoma (EA) is a rare, highly invasive tumor. The histopathological features of EA are not distinct and less reported in the literature, and most of the medical records are incomplete.
PATIENT CONCERNS: A 61-year-old woman who came to the hospital because of pain in her right hip. This patient had had surgery for right hip tuberculosis 30 years ago.
DIAGNOSES: The present study reports a case of primary EA of bone with aneurysmal bone cyst (ABC) that was diagnosed by 3 experienced pathologists.
INTERVENTIONS: The patients had undergone 2 surgeries; however, an early recurrence of the tumor was caused the death of the patient.
OUTCOMES: Ten EA cases from other literature were reviewed in this article; all the symptoms were found in different parts of bone, and the case data were relatively complete. The primary clinical features and nonspecific histopathological morphology of the disease were summarized from the 11 cases mentioned in the literature, and the main immunohistochemistry characteristics and diagnostic traps of EA were reviewed.
LESSONS: Because the tumor has no characteristic diagnostic index in imaging and laboratory examination, the histopathologic features are not typical, especially in the case of obvious secondary lesions. It is easy to miss and misdiagnose. If possible, the diagnosis should be combined with immunohistochemical results.

Abstract
This PDQ cancer information summary has current information about the treatment of childhood vascular tumors. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board.

The poor prognosis of the primary gastric epithelioid angiosarcoma: A case report.

Medicine (Baltimore). 2018 Apr;97(15):e0287

Authors: Xia J, Shi D, Wu Z, Chen Y, Liu B, Chen L, Metta W, Zheng Y

Abstract
RATIONALE: Primary gastric epithelioid angiosarcoma is a highly aggressive endothelial cell malignancy and may pose a great diagnostic challenge.
PATIENT CONCERNS: Here we describe the case of a 56-year-old man presented with melena and epigastric dull pain for 2 weeks.
DIAGNOSIS: Primary gastric epithelioid angiosarcomas: the definitive diagnosis was provided by immunohistochemical analysis with endothelial markers such as cluster of differentiation 31 (CD31), ether-a-go-go-related gene (ERG), and Freund leukemia integration (FLI-1).
INTERVENTIONS: After gastroscopic biopsy was performed at the bleeding fundus and the results suggested malignant tumor, radical gastrectomy was performed.
OUTCOMES: Unfortunately, regional lymph node enlargement and distant metastases occurred about 1 month later. The patient did not have the opportunity to undergo chemotherapy or other treatment and died from multiple organ dysfunction syndrome.
LESSONS: Primary gastric epithelioid angiosarcomas are rare tumors with a high rate of lymph nodes and peripheral organs metastasis. The strong cytokeratin expression in epithelioid angiosarcomas represents a diagnostic pitfall for pathologists. Their clinical behaviors are unpredictable and results with surgical excision alone have been disappointing. Thus, the prognosis is generally considered poor and patients seldom can survive over 1 year after diagnosis.

Epithelioid hemangioma of bone: a report of two special cases and a literature review.

Skeletal Radiol. 2016 Dec;45(12):1723-1727

Authors: Zhou Q, Lu L, Fu Y, Xiang K, Xu L

Abstract
Intraosseous epithelioid hemangioma (EH) is a rare intermediate vascular neoplasm, characterized by locally aggressive and rarely metastasizing behavior. Occasionally, EH of bone can behave strangely and may simulate malignant neoplasm. Here, we report two cases of EH of bone. Of interest was the fact that the computed tomography and magnetic resonance images from one case showed an osteolytic lesion in the right scapula, with multiple swollen lymph nodes in the right supraclavicular and axillary areas. Another patient exhibited a local recurrence in the cervical vertebrae. The initial radiological diagnosis of both cases was metastatic tumor. EH should be included in the differential diagnosis of a radiographic osteolytic lesion with an aggressive appearance. Also, we reviewed the literature that reported EH of bone and summarized their radiological appearances. The cases of EH of bone that exhibited involvement of regional or draining lymph nodes were also summarized.

Abstract
Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of early childhood and infancy. Kasabach-Merritt phenomenon, a common complication of KHE, is characterized by life-threatening thrombocytopenia, hemolytic anemia, and consumption coagulopathy. There may be atypical cases that do not present with Kasabach-Merritt phenomenon and do have atypical imaging findings. Knowledge of atypical imaging features may assist radiologists in identifying KHE. In this report, we present a 4-year-old case of KHE with atypical ultrasound findings.

Unicentric epithelioid hemangioendothelioma of the calcaneus: a case report and review of literature.

Clin Sarcoma Res. 2018;8:5

Authors: Plumby MC, Bacaj P, Lindsey BA

Abstract
Background: This review of the literature combined with a clinical case will allow the illustration of a favorable outcome of this variable low grade malignancy, display a role for limb salvage surgery with intralesional treatment, and offer a clinical example of epithelioid hemangioendothelioma, a rare malignancy.
Case presentation: The case report presents a case of solitary epithelioid hemangioendothelioma (EHE) of the calcaneus in a 60-year-old male. Primary vascular tumors of the bone are rare; however, EHE is one of the most common primary malignant vascular tumors to occur in bone. A review of the literature found few cases that involved the calcaneus; those cases found that involved the calcaneus were either part of a multifocal or metastatic disease process. Our case presents a 45-month clinical follow-up of solitary EHE in the calcaneus treated with surgical excision by curettage and cementing.
Conclusion: This case has clinical follow-up greater than 2 years post-operatively and could be a guide for treatment of a rare disorder with a substantial paucity of literature.

Abstract
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood soft tissue sarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Abstract
This PDQ cancer information summary has current information about the treatment of childhood soft tissue sarcoma. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care. Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board.

A Case Report of 2 Sirolimus-Related Deaths Among Infants With Kaposiform Hemangioendotheliomas.

Pediatrics. 2018 Apr;141(Suppl 5):S425-S429

Authors: Ying H, Qiao C, Yang X, Lin X

Abstract
Kaposiform hemangioendothelioma (KHE) is a rare infiltrative vascular tumor that is potentially life-threatening when presenting with Kasabach-Merritt phenomenon (KMP). KMP is clinically characterized as severe thrombocytopenia and hypofibrinogenemia and therefore is associated with a high mortality rate. There is no standard of cure for KHE currently. Potential medications, including corticosteroids, propranolol, and chemotherapy drugs such as sirolimus, are often used for alleviating KHE symptoms. Although some case reports of sirolimus treatment have shown promising results with recovered coagulant parameters, the off-target effects may cause severe problems. Here we describe 2 cases of infant patients with KHE and KMP who were scheduled to receive sirolimus on a long-term basis. However, both patients developed paroxysmal cough and tachypnea shortly after the onset of sirolimus treatment and succumbed to infection thereafter. This report reveals a potential risk of infection in sirolimus-treated infant patients. The fatal complication highlights the importance of antibiotic prophylaxis and serum sirolimus level monitoring to ensure the safe use of sirolimus in the treatment of infant patients with KHE.

Abstract
Sirolimus is an effective therapy for children with kaposiform hemangioendothelioma with or without the Kasabach-Merritt phenomenon. We report the case of a child with kaposiform hemangioendothelioma and the Kasabach-Merritt phenomenon who developed Pneumocystis carinii pneumonia (PCP) while on sirolimus and a prednisolone taper, after lack of adequate response to prednisolone, propranolol, and vincristine. He had a prompt positive clinical and laboratory response to sirolimus, but 4 weeks after starting it, at the age of 4 months, he developed PCP. This led to respiratory failure, which required extracorporeal membrane oxygenation. Sirolimus was temporarily discontinued, and he was successfully treated for PCP with sulfamethoxazole-trimethoprim and methylprednisolone. He was restarted on sirolimus 3 weeks after discharge and given sulfamethoxazole-trimethoprim prophylaxis. At the age of 22 months, while still on sirolimus, the lesion continued to improve with test results revealing stable hemoglobin and platelet counts. PCP is a rare but life-threatening side effect of sirolimus therapy, especially in the setting of concurrent steroid treatment. Pneumocystis prophylaxis should be considered for patients receiving sirolimus.

18F-FDG PET/CT of Secondary Epithelioid Angiosarcoma of the Proximal Femur in a Patient With Polyostotic Fibrous Dysplasia.

Clin Nucl Med. 2017 Oct;42(10):e454-e456

Authors: Hakozaki M, Yamada H, Hasegawa O, Watanabe K, Konno S

Abstract
Fibrous dysplasia rarely transforms into a secondary malignancy. We present the PET/CT findings at pretreatment and posttreatment in an exceedingly rare case of epithelioid angiosarcoma of the bone secondary to polyostotic fibrous dysplasia.

Abstract
BACKGROUND: Few studies have reported the clinical features, complications and predictors of Kasabach-Merritt phenomenon (KMP) associated with Kaposiform haemangioendothelioma (KHE).
OBJECTIVES: To determine the clinical characteristics present at diagnosis and to identify features that may aid clinicians in managing KHE.
METHODS: We conducted a cohort study of 146 patients diagnosed with KHE.
RESULTS: KHE precursors or lesions were present at birth in 52.1% of patients. In 91.8% of patients, lesions developed within the first year of life. The median age at diagnosis of KHE was 2.3 months (interquartile range 1.0-6.0). The extremities were the dominant location, representing 50.7% of all KHEs. Among KHEs in the cohort, 63.0% were mixed lesions (cutaneous lesions with deep infiltration). Approximately 70% of patients showed KMP. A KHE diagnosis was delayed by ≥ 1 month in 65.7% of patients with KMP. Patients with KMP were more likely to have major complications than patients without KMP (P = 0.023). Young age (< 6 months), trunk location, large lesion size (> 5.0 cm) and mixed lesion type were associated with KMP in a univariate analysis. In the multivariate analysis, only age [odds ratio (OR) 11.9, 95% confidence interval (CI) 4.07-34.8; P < 0.001], large lesion size (OR 5.08, 95% CI 2.24-11.5; P < 0.001) and mixed lesion type (OR 2.96, 95% CI 1.23-7.13; P = 0.016) were associated with KMP.
CONCLUSIONS: Most KHEs appeared before 12 months of age. KHEs are associated with various major complications, which can occur in combination and develop early in the disease process. Young age, large lesion size and mixed lesion type are important predictors of KMP. This article is protected by copyright. All rights reserved.

Abstract
Vascular tumors in infants present a diagnostic and treatment dilemma for both clinicians and pathologists. Infantile hemangioma, the most common vascular tumor in infants, can be confused for other less common vascular tumors in infants. Correct and timely diagnosis is important, as some vascular tumors can be associated with life-threatening coagulopathy. We present the cases of 5 vascular tumors that have clinical and histologic overlap: infantile hemangioma, pyogenic granuloma, noninvoluting congenital hemangioma, tufted angioma, and kaposiform hemangioendothelioma. Typical clinical and histopathologic features of each lesion are summarized. We review the utility and characteristic immunohistochemistry including CD31, CD34, GLUT-1, D2-40, LYVE-1, Prox-1, and WT-1. Collaboration between the clinician and the dermatopathologist correlating the clinical history and histopathologic features can lead to the correct diagnosis, whereas the utility of immunohistochemistry remains in question.

Abstract
OPINION STATEMENT: Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma, as such it can pose a clinical dilemma based solely on its rarity. Also, the spectrum of disease varies greatly between an indolent disease and aggressive disease with widespread metastases. In our clinical practice, the primary focus has been to get a handle on the aggressive nature of the disease, which will then dictate how urgently one needs to treat the patient. Pathological review with immunohistochemistry and molecular characterization is paramount. Our treatment strategy is watch-and-wait versus active therapy on clinical trial or based on results of prior clinical trials. There is evidence to support the use of chemotherapeutics and targeted therapies specifically focusing on anti-angiogenesis. The current landscape of oncology with the emergence and excitement of immunotherapy could also translate in a role for immunotherapy in this disease. While rare, there is certainly no reason that research and trials for patients with EHE should not remain on utmost importance for those of us who specialize in the treatment of sarcomas.

Abstract
BACKGROUND: Accurate distinction of epithelioid hemangioma (EH) from its malignant mimics is paramount but it remains challenging due to its wide morphological spectrum and lack of objective molecular markers. FOSB oncogenic activation was recently identified as a key event in endothelial proliferation. We sought to investigate the FOSB staining pattern in EH with angiolymphoid hyperplasia with eosinophilia morphology (EH-AHLE) and to evaluate its value in differential diagnosis of epithelioid vascular tumors.
METHODS: From the authors' files, 15 representative cases of EH-ALHE were selected and evaluated for their FOSB immunostaining pattern. Other vascular proliferations which can be morphological mimics were also tested: epithelioid hemangioendothelioma (EHE) (5 cases) and epithelioid angiosarcoma (EAS) (5 cases).
RESULTS: All 15 cases of EH-ALHE showed strong and homogeneous FOSB nuclear positivity in endothelial cells with ample cytoplasm and intracytoplasmic vacuoles. All cases of EHE and EAS lacked FOSB immunoreactivity or showed only incidental weak FOSB immunoreactivity in less than 5 nuclei per lesion.
CONCLUSIONS: FOSB immunohistochemistry is sensitive in the diagnosis of EH-ALHE, and allows differentiation from its histological mimics. An immunohistochemical panel including not only pan-cytokeratin AE1/AE3 and endothelial markers, but also FOSB, helps in the diagnosis of epithelioid vascular tumors.

Abstract
PURPOSE: Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare locally aggressive neoplasm with endothelial differentiation, which often presents with multiple lesions. These tumors have characteristic SERPINE1-FOSB fusions. We report a 17 years old patient with advanced unresectable PHE with a durable complete remission to the multi-tyrosine kinase inhibitor telatinib. The aim of this study was to generate an in vitro model for PHE, to study the functional consequences of SERPINE1-FOSB in endothelial cells, and its interaction with telatinib, to biologically substantiate the complete response to telatinib.
EXPERIMENTAL DESIGN: As the fusion results in overexpression of a truncated form of FOSB, we overexpressed truncated FOSB in normal endothelial cells.
RESULTS: Truncated FOSB significantly affected tumor growth in 3D on matrigel with increased and sustained sprouting. Moreover, truncated FOSB acted as an active transcription factor capable to regulate its own transcription, as well as to upregulate PDGFRA and FLT1 expression (4-fold). Telatinib decreased proliferation and tumor growth in 3D and induced apoptosis. As expected, telatinib blocked VEGF signaling as phosphorylation of ERK was abolished. Interestingly, in FOSB overexpressing cells, telatinib specifically affected PDGFRA, FLT1 and FLT4 signaling and down-regulated SERPINE1, thereby affecting the self-regulation of the fusion gene.
CONCLUSIONS: We provide a biological substantiation of a complete clinical remission that was seen in a patient with PHE, showing that telatinib indirectly interferes with the self-regulated expression of the fusion product. Thus, telatinib or any other currently available VEGFR1-4/PDGFRA inhibitor, could be a highly specific treatment option for patients with multifocal unresectable PHE.